Mutations of PTPN23 in developmental and epileptic encephalopathy

N. Sowada, M.O. Hashem, R. Yilmaz, M. Hamad, N. Kakar, H Thiele, S.T Arold, H. Bode, F.S Alkuraya, G. Borck
Human Genetics, volume 136, issue 11-12, pp. 1455-1461, (2017)

Mutations of PTPN23 in developmental and epileptic encephalopathy


Mutations, PTPN23, Eepileptic, Encephalopathy


​Developmental and epileptic encephalopathies (DEE) are a heterogeneous group of neurodevelopmental disorders with poor prognosis. Recent discoveries have greatly expanded the repertoire of genes that are mutated in epileptic encephalopathies and DEE, often in a de novo fashion, but in many patients, the disease remains molecularly uncharacterized. Here, we describe a new form of DEE in patients with likely deleterious biallelic variants in PTPN23. The phenotype is characterized by early onset drug-resistant epilepsy, severe and global developmental delay, microcephaly, and sometimes premature death. PTPN23 encodes a tyrosine phosphatase with strong brain expression, and its knockout in mouse is embryonically lethal. Structural modeling supports a deleterious effect of the identified alleles. Our data suggest that PTPN23 mutations cause a rare severe form of autosomal-recessive DEE in humans, a finding that requires confirmation.


DOI: 10.1007/s00439-017-1850-3


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